HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium

So Ri Kim, Kyung Sun Lee, Hee Sun Park, Seoung Ju Park, Kyung-Hoon Min, Hee Moon, Kamal D. Puri, Yong Chul Lee

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses. One of the HIF-1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA-treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF-1α activation and the role of HIF-1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110d isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation.

Original languageEnglish
Pages (from-to)2858-2869
Number of pages12
JournalEuropean Journal of Immunology
Volume40
Issue number10
DOIs
Publication statusPublished - 2010 Oct 1
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor A
Epithelium
Phosphatidylinositol 3-Kinases
Epithelial Cells
Inhalation
Inflammation
Airway Remodeling
Cell Hypoxia
Lung
Interleukin-13
Interleukin-5
Capillary Permeability
Interleukin-4
Allergens
Small Interfering RNA
Transfection
Blood Vessels
Protein Isoforms
Cell Count

Keywords

  • Allergic airway disease
  • Hypoxia-inducible factor-1α
  • PI3K-δ
  • RNA interference
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium. / Kim, So Ri; Lee, Kyung Sun; Park, Hee Sun; Park, Seoung Ju; Min, Kyung-Hoon; Moon, Hee; Puri, Kamal D.; Lee, Yong Chul.

In: European Journal of Immunology, Vol. 40, No. 10, 01.10.2010, p. 2858-2869.

Research output: Contribution to journalArticle

Kim, So Ri ; Lee, Kyung Sun ; Park, Hee Sun ; Park, Seoung Ju ; Min, Kyung-Hoon ; Moon, Hee ; Puri, Kamal D. ; Lee, Yong Chul. / HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium. In: European Journal of Immunology. 2010 ; Vol. 40, No. 10. pp. 2858-2869.
@article{5caab4faf84c404b861a84b8dc14c738,
title = "HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium",
abstract = "Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses. One of the HIF-1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA-treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF-1α activation and the role of HIF-1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110d isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation.",
keywords = "Allergic airway disease, Hypoxia-inducible factor-1α, PI3K-δ, RNA interference, Vascular endothelial growth factor",
author = "Kim, {So Ri} and Lee, {Kyung Sun} and Park, {Hee Sun} and Park, {Seoung Ju} and Kyung-Hoon Min and Hee Moon and Puri, {Kamal D.} and Lee, {Yong Chul}",
year = "2010",
month = "10",
day = "1",
doi = "10.1002/eji.200939948",
language = "English",
volume = "40",
pages = "2858--2869",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "10",

}

TY - JOUR

T1 - HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium

AU - Kim, So Ri

AU - Lee, Kyung Sun

AU - Park, Hee Sun

AU - Park, Seoung Ju

AU - Min, Kyung-Hoon

AU - Moon, Hee

AU - Puri, Kamal D.

AU - Lee, Yong Chul

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses. One of the HIF-1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA-treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF-1α activation and the role of HIF-1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110d isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation.

AB - Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses. One of the HIF-1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA-treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF-1α activation and the role of HIF-1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110d isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation.

KW - Allergic airway disease

KW - Hypoxia-inducible factor-1α

KW - PI3K-δ

KW - RNA interference

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=77957102906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957102906&partnerID=8YFLogxK

U2 - 10.1002/eji.200939948

DO - 10.1002/eji.200939948

M3 - Article

C2 - 20827786

AN - SCOPUS:77957102906

VL - 40

SP - 2858

EP - 2869

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -